The past decade has seen a rapid increase in the application of brain stimulation devices to treat a variety of movement disorders and other neuropathologies. Present noninvasive technologies suffer from fundamental limitations and have yet to reach the level of efficacy of invasive methods, such as deep brain stimulation. Electromechanical Stimulation (EMS) is an improved noninvasive modality, which offers the potential of noninvasive deep brain stimulation. Preliminary experiments with this technique have revealed improved focality and penetration compared to other forms of noninvasive stimulation. The work proposed in this study will explore fundamental efficacy and safety criteria related to the technique. The first study component will evaluate the efficacy of EMS, where recordings will be made of the combined local visual evoked potential (VEP)/ electroencephalogram (EEG) from area 17 of anaesthetized adult cats immediately following electromechanical stimulation and compared with baseline, SHAM stimulation, transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and mechanical stimulation (MS). A statistical analysis will be performed to characterize the signal properties of the VEP/EEG data and determine the effect of electromechanical stimulation on neural response (as a function of magnitude, depth, and duration of effect). It is hypothesized that electromechanical stimulation will result in a significantly larger amplification of the VEP response and power in the EEG signal relative to the other methods of stimulation, a measurable effect in deep brain regions for which other stimulation methods are ineffective, and a significantly longer response duration in comparison to these other techniques. The second component of the study, focused on the safety of the technique, will assess tissue temperature and histology changes to electromechanical stimulation. Animal cortices will be exposed to extended durations of EMS stimulation and evaluated for thermodynamic changes, via implanted micro-thermocouple measurements, and histological changes, via an array of histological staining methods to look for patterns of cell loss or gliosis, and white matter damage and degeneration (myelin). We hypothesize that electromechanical stimulated tissue will be indistinguishable from the non-stimulated tissue and that tissue temperature changes from stimulation will be physiologically insignificant. The final component of this study will assess EMS's efficacy in modifying functional patterns of brain activity by means of high resolution 14[C]2-deoxyglucose imaging (2DG). We will compare these results to 2-DG data previously developed for other stimulation modalities (such as TMS and tDCS) to assess the metabolic and functional effects of EMS (in terms of magnitude, focality, and time). We hypothesize that EMS will demonstrate greater focality, depth of penetration, and magnitude of effect compared to other simulation modalities. Future developments with this technology could provide a platform for innovative and improved neurological treatments while simultaneously providing a tremendous market opportunity. PUBLIC HEALTH RELEVANCE Brain stimulation devices are used to treat a variety of neurologic and psychiatric disorders. Highland Instruments' Electromechanical Stimulation (EMS) is a noninvasive neurostimulation method which improves upon current noninvasive technologies with superior focality, targeting control, and penetration, and for the first time offers the possibility of noninvasive deep brain stimulation (i.e., stimulating deep brain structures without maximally stimulating the surface). The technology could benefit patients with movement disorders and other neuropathologies who are currently not served by present noninvasive options. [unreadable] [unreadable] [unreadable]